Diabetes Mellitus:- Part 1 – Carbohydrate (CHO) and Glucose Metabolism, Insulin and Glucagon

Carbohydrate (CHO) and Glucose Metabolism

What Sample for Glucose Estimation is needed?

1. This test can be done on serum. The serum should be separated within 30 minutes of collection.
2. The Serum can be stored at 25 °C for 8 hours and at 4 °C for 72 hours.
3. Oxalated blood can also be used. Preservative sodium fluoride may be added.
4. The plasma can be stored at 25 °C for 24 hours (with preservative sodium fluoride).

What are the factors for the Stability of the glucose level?

1. One milliliter of blood in an anticoagulant containing fluoride will remain stable for 3 hours.
2. Oxalate plasma is stable at 2 to 8 °C for 48 hours.
3. Serum is mainly used; it is stable for 8 hours at 25 °C and 72 hours at 4 °C.
4. A 6- to 8-hour fast is required for a fasting sample.

What are the Indications for glucose estimation?

1. This test is done to diagnose diabetes mellitus.
2. This test is also done to evaluate and monitor diabetes mellitus.

How will you discuss the pathophysiology of the Carbohydrates (CHO)?

1. Carbohydrates are major dietary components and an essential energy source.
   1. Glucose is controlled by insulin and glucagon.
   2. Glucose is low in the fasting state.
   3. The glucose = C₆H₁₂O₆ = C₆ (H₂O)6.
   4. Lactose = C₁₂H₂₂O₁₁ = C₁₂ (H₂O)_11.
2. The capacity of the body to store carbohydrates is limited:
   1. The liver can store only 10% of its wet weight.
   2. Muscles can store 5% of their wet weight.
   3. This store amount is only sufficient for half a day.
3. Carbohydrates include sugar and starch.
4. The salivary gland enzyme converts starch and glycogen into dextrin and maltose.
   1. The acidic pH of the stomach inhibits salivary amylase.
   2. Pancreatic alkaline secretion of amylase acts mainly on maltose and the disaccharides.
5. Maltose, lactose, and sucrose are converted into:
   1. Glucose.
   2. Galactose.
   3. Fructose.

What are the functions of carbohydrates (CHO)?

1. CHO is a component of RNA and DNA.
2. CHO is the Source of energy, which is glucose.
3. Under fasting conditions, the following organs depend only upon glucose as a source of energy:
   1. The brain is the main organ dependent on glucose.
   2. Red blood cells.
   3. White blood cells.
   4. Platelets.
   5. Kidney medulla.

Carbohydrate and Glucose Metabolism: Carbohydrate (CHO) functions

4. Increased glucose level leads to its storage as glycogen in the liver.
   1. Decreased glucose level leads to glycogenolysis and forms glucose from the glycogen.

How will you discuss glucose metabolism?

1. The breakdown of the following sources forms glucose:
   1. Grains.
   2. Starchy vegetables.
   3. Legumes.
   4. The body stores glycogen.
   5. Endogenous proteins.
   6. Excess glucose is converted into fat by adipose cells and stored in the adipose tissue.

Glucose pathways

2. The Triose pathway is the main junction where four pathways intersect and help maintain glucose levels.
   1. This is a complex enzymatic system, but glucose levels remain within the normal range.

Glucose triose pathway

3. The following diagrams illustrate that glucose metabolism is closely linked to the metabolism of fats and proteins.
4. Glucose levels are controlled by insulin and glucagon.

Glucose, Insulin, and Glucagon Metabolism

Glucose metabolism and the role of the liver

Carbohydrate metabolism

Pathophysiology of Glucagon and Insulin

Glucagon:

How will you define glucagon?

1. Glucagon is produced by the Alpha (α) cells of the islets of Langerhans in the pancreas.
2. Glucagon is a 29-amino acid polypeptide.

Insulin and Glucagon Production

What is the role of Glucagon?

1. The major target organ is the liver, which binds to a specific receptor and increases intracellular adenosine-5-monophosphate and calcium.
2. Glucagon stimulates the production of glucose in the liver by glycogenolysis and gluconeogenesis.
3. It also increases hepatic ketogenesis.
4. The minor target organ is fat, which causes lipolysis.
5. Glucagon secretion is controlled by glucose level.
   1. A low glucose level is stimulatory.
   2. A high glucose level is inhibitory.
6. During fasting, protein and fat are broken down into glucose under the influence of Glucagon.
7. In the case of long-standing diabetes mellitus, it impairs the glucagon response to hypoglycemia, leading to increased chances of hypoglycemia episodes.
8. Insulin inhibits glucagon secretion from the pancreas.

Insulin:

How will you define Insulin and its action?

1. Insulin is produced by the beta cells of the islets of Langerhans in the pancreas.
2. Insulin is an anabolic hormone.
3. First, proinsulin is formed in the ribosomes of the rough endoplasmic reticulum.
4. Later on, stored in the Golgi apparatus.
5. Proteolytic cleavage forms Insulin and C-peptide.

Insulin formation and proinsulin

What is the role of Insulin and Diabetes Mellitus?

1. It results from the abnormality in the production or use of insulin.
2. β-cells of the pancreas produce insulin, and the abnormality of these Β-cells leads to diabetes mellitus:
   1. β-cells’ insulin production is deficient.
   2. Normal synthesis but abnormal release.
   3. Extra-pancreatic factors, such as peripheral tissue cell receptor dysfunction, can lead to resistance to insulin’s cellular action.
   4. Non-pancreatic hormones will affect insulin secretion or blood glucose metabolism.
3. C-peptide has no biological activity and has a longer life than insulin.
   1. 1. Fasting C-peptide concentration is fivefold to 10fold higher than insulin.

C-peptide and Proinsulin

What is the action of Insulin on the cells?

1. Insulin binds to insulin receptors in muscle, liver, and fat cells.
2. Insulin facilitates the uptake of glucose into cells, where it is metabolized into glycogen, amino acids, and fatty acids.
3. Insulin lowers the plasma glucose level.

Insulin functions

4. Increased insulin lowers blood glucose levels, and a deficiency increases glucose levels.

Insulin action on the tissue

Glucose and glucagon metabolism

5. Other hormones, such as adrenocorticosteroids, ACTH, epinephrine, and thyroxine, can also affect glucose metabolism.
   1. The above hormones increase the plasma glucose level.
6. Serum glucose levels are dependent on the time and relation to food intake.
7. The glucose level is low in the fasting state.
   1. Glucose goes to the normal state after 2 hours of food intake.
8. The concentration of glucose is higher in arterial blood than in venous blood.
9. When fasting glucose is around 126 mg/dl, try to estimate the glucose level after an oral 75-gram glucose load.
   1. Now check the one-hour and two-hour samples.
   2. This oral glucose test will identify cases of Impaired Glucose Tolerance, allowing you to prevent the development of Diabetes Mellitus.
   3. The fasting level is between 100 to 126 mg/dl, which is called fasting hyperglycemia.
   4. The glucose level of 135 mg/dL is abnormal in the fasting state but returns to normal one hour after the meal.

What are the Lab findings in hyperglycemia (Diabetes mellitus)?

1. Increased blood glucose.
2. Increased urine-specific gravity.
3. Decreased blood and urine pH values (acidosis).
4. Increased blood and urine osmolality.
5. Electrolyte disturbance.
6. Ketones in the blood and urine.

Questions and answers: